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Neonatal Immunization against Gonadotropin-Releasing Hormone (GnRH) Results in Diminished GnRH Secretion in Adulthood

Prince Henry’s Institute of Medical Research (I.J.C., V.V.T., A.R.), Clayton, Victoria 3168, Australia; Commonwealth Scientific and Industrial Research Organisation Division of Animal Production (B.W.B.), Blacktown, New South Wales 2148, Australia; Department of Physiology (C.J.S.), Monash University, Clayton, Australia; Victorian Institute of Animal Science (R.F.), Department of Natural Resources and Energy, Werribee 3030, Australia; and Medical Research Council Research Unit for Molecular Reproductive Endocrinology (R.P.M.), Regulatory Peptides Research Unit, Department of Chemical Pathology, University of Cape Town, Cape Town, South Africa

Address all correspondence and requests for reprints to: I. J. Clarke, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: iain.clarke{at}med.monash.edu.au

The effects of neonatal immunization against GnRH were studied in sheep after they had reached adulthood (3–4 yr) and the antibody titers had fallen to undetectable levels. The immunized animals had small gonads, and the females did not have large follicles (>3 mm) or corpora lutea in their ovaries. Compared with controls, the immunized animals had low or nondetectable levels of LH and FSH in peripheral plasma, and the immunized animals generally failed to respond to a single iv GnRH challenge. After ovariectomy, the control ewes, but not the immunized ewes, showed an elevation in plasma LH and FSH levels. The sampling of hypophysial portal blood, with a newly described method, showed that the secretion of GnRH was reduced in the immunized animals, but the amount of GnRH in the median eminence was similar in the control and immunized ewes. The pituitary content of LH and FSH was reduced in the immunized ewes as was messenger RNA for the gonadotropin subunits and the GnRH receptor. These data indicate that neonatal immunization does not affect the synthesis of GnRH in adulthood but reduces the secretion of GnRH, causing long-term sterility in these animals.

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